Bupropion SR vs XR for Augmenting Sertraline 200mg
Use bupropion SR (sustained release) as the augmenting agent for sertraline 200mg, as this is the only formulation with established evidence for augmentation therapy in depression. 1
Evidence-Based Rationale
Guideline Support for Bupropion SR Augmentation
The American College of Physicians' 2023 systematic review and network meta-analysis specifically evaluated bupropion SR for augmentation of SSRIs in patients who failed to achieve remission. 1 The landmark STAR*D trial demonstrated that augmenting citalopram with bupropion SR showed similar efficacy to other augmentation strategies, with a significant safety advantage—only 12.5% discontinued due to adverse events compared to 20.6% with buspirone augmentation (P < 0.001). 1
Why Not Bupropion XR?
No evidence exists for bupropion XR (extended release) as an augmentation agent. 1 The clinical trials evaluating bupropion for augmentation therapy exclusively used the SR formulation. 1, 2 While bupropion XR is FDA-approved for major depressive disorder as monotherapy, its efficacy was established in only 2 of 6 well-designed placebo-controlled studies as a primary treatment, not as augmentation. 3
Pharmacokinetic Considerations
All three bupropion formulations (IR, SR, XR) are bioequivalent in terms of systemic exposure to bupropion, but differ in dosing frequency and peak-to-trough ratios. 3 However, the SR formulation's twice-daily dosing was specifically studied and validated in augmentation protocols, making it the evidence-based choice. 1, 2
Practical Implementation
Dosing Protocol for Bupropion SR Augmentation
- Continue sertraline 200mg unchanged 1
- Start bupropion SR at 150mg once daily in the morning 2
- After 3-7 days, increase to 150mg twice daily (total 300mg/day) if tolerated 2
- Maximum dose: 200mg twice daily (total 400mg/day), though most studies used 150-300mg/day 2
Timeline for Response Assessment
- Evaluate response at 6 weeks of augmentation therapy 2
- 54% of patients in prospective trials achieved ≥50% reduction in depression scores by week 6 2
- If no meaningful improvement by 6-8 weeks, consider alternative strategies 1
Safety Monitoring
Key Adverse Events to Monitor
- Seizure risk: Bupropion lowers seizure threshold; avoid in patients with epilepsy or seizure history 1
- Blood pressure: Monitor vital signs as bupropion can increase blood pressure 1
- Insomnia: Take second dose no later than mid-afternoon to minimize sleep disruption 1
- Activation symptoms: Anxiety, agitation, or restlessness may occur initially 4
Advantages of This Combination
The sertraline-bupropion combination targets complementary neurotransmitter systems: sertraline inhibits serotonin reuptake while bupropion inhibits norepinephrine and dopamine reuptake without significant serotonergic effects. 3, 5 This synergistic mechanism may explain efficacy in treatment-refractory depression. 5
Common Pitfalls to Avoid
- Using bupropion XR instead of SR: No augmentation data exists for XR formulation; stick with the evidence-based SR formulation 1, 2
- Inadequate trial duration: Patients need at least 6 weeks at therapeutic doses before declaring treatment failure 2
- Exceeding maximum daily dose: Total bupropion dose should not exceed 400mg/day due to dose-dependent seizure risk 1, 3
- Combining with opioids: If using naltrexone-bupropion formulations (not applicable here), avoid in patients requiring opioid therapy 1
- Expecting immediate results: Like most antidepressant strategies, augmentation requires 4-6 weeks for full therapeutic effect 2
Alternative Considerations
If bupropion SR augmentation fails or is contraindicated, the American College of Physicians found that switching to a different antidepressant (escitalopram, duloxetine, venlafaxine XR) or augmenting with cognitive therapy showed similar efficacy, with cognitive therapy potentially having fewer adverse events. 1